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1.
Front Neurol ; 15: 1403551, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827576

RESUMO

Introduction: Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the follow-up of patients with SARS-CoV-2-related autonomic imbalance are available. Methods: In this study, we conducted a comprehensive clinical and functional follow-up on healthcare workers (HCWs) with former mild COVID-19 (group 1, n = 67), to delineate the trajectory of post-acute autonomic imbalance, we previously detected in a case-control study. Additionally, we assessed HCWs for which a test before SARS-CoV-2 infection was available (group 2, n = 29), who later contracted SARS-CoV-2, aiming to validate findings from our prior case-control investigation. We evaluated autonomic nervous system heart modulation by means of time and frequency domain heart rate variability analysis (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings, were obtained at about 6, 13 months and both at 6 and 13 months from the negative SARS-CoV-2 naso-pharyngeal swab (NPS) for group 1 and at about 1-month from the negative NPS for group 2. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded. Results: Group 1 was split into three subgroups clinically and functionally followed at, about 6 months (subgroup-A, n = 17), 13 months (subgroup-B, n = 37) and both at 6 and 13 months (subgroup-C, n = 13) from the negative SARS-CoV-2 NPS. In subgroup-A, at 6-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed an increase in normalized high frequency power (nHF) (t = 2.99, p = 0.009), a decrease in the normalized low frequency power (nLF) (t = 2.98, p = 0.009) and in the LF/HF ratio (t = 3.13, p = 0.006). In subgroup B, the comparison of the spectral components in the frequency domain HRV parameters, at 13-month follow-up compared with baseline, showed an increase in nHF (t = 2.54, p = 0.02); a decrease in nLF (t = 2.62, p = 0.01) and in the LF/HF ratio (t = 4.00, p = 0.0003). In subgroup-C, at both 6 and 13-month follow-ups, the spectral components in the frequency domain HRV parameters were higher than baseline in nHF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively); lower in nLF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively), and in LF/HF (t = 1.92, p = 0.08 and (t = 2.43, p = 0.03, respectively). A significant proportion of HCWs reported persistent COVID-19 symptoms at both the 6 and 13-month follow-ups, seemingly unrelated to cardiac autonomic balance. In group 2 HCWs, at 1-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed a decrease in nHF (t = 2.19, p = 0.04); an increase in nLF (t = 2.15, p = 0.04) and in LF/HF (t = 3.49, p = 0.002). Conclusion: These results are consistent with epidemiological data suggesting a higher risk of acute cardiovascular complications during the first 30 days after COVID-19. The SARS-CoV-2 associated autonomic imbalance in the post-acute phase after recovery of mild COVID-19 resolved 6 months after the first negative SARS-CoV-2 NPS. However, a significant proportion of HCWs reported long-term COVID-19 symptoms, which dot not seems to be related to cardiac autonomic balance. Future research should certainly further test whether autonomic imbalance has a role in the mechanisms of long-COVID syndrome.

2.
JACC Cardiovasc Imaging ; 17(5): 533-551, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38597854

RESUMO

Population aging is one of the most important demographic transformations of our time. Increasing the "health span"-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.


Assuntos
Envelhecimento , Doenças Cardiovasculares , Sistema Cardiovascular , Valor Preditivo dos Testes , Humanos , Envelhecimento/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/fisiopatologia , Sistema Cardiovascular/metabolismo , Fatores Etários , Idoso , Envelhecimento Saudável , Prognóstico , Pessoa de Meia-Idade , Feminino , Masculino , Idoso de 80 Anos ou mais , Animais , Senescência Celular
3.
J Cachexia Sarcopenia Muscle ; 15(3): 770-780, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38553412

RESUMO

Sarcopenia, a musculoskeletal disease characterized by the progressive loss of skeletal muscle mass, strength, and physical performance, presents significant challenges to global public health due to its adverse effects on mobility, morbidity, mortality, and healthcare costs. This comprehensive review explores the intricate connections between sarcopenia and low birth weight (LBW), emphasizing the developmental origins of health and disease (DOHaD) hypothesis, inflammatory processes (inflammaging), mitochondrial dysfunction, circadian rhythm disruptions, epigenetic mechanisms, and genetic variations revealed through genome-wide studies (GWAS). A systematic search strategy was developed using PubMed to identify relevant English-language publications on sarcopenia, LBW, DOHaD, inflammaging, mitochondrial dysfunction, circadian disruption, epigenetic mechanisms, and GWAS. The publications consist of 46.2% reviews, 21.2% cohort studies, 4.8% systematic reviews, 1.9% cross-sectional studies, 13.4% animal studies, 4.8% genome-wide studies, 5.8% epigenome-wide studies, and 1.9% book chapters. The review identified key factors contributing to sarcopenia development, including the DOHaD hypothesis, LBW impact on muscle mass, inflammaging, mitochondrial dysfunction, the influence of clock genes, the role of epigenetic mechanisms, and genetic variations revealed through GWAS. The DOHaD theory suggests that LBW induces epigenetic alterations during foetal development, impacting long-term health outcomes, including the early onset of sarcopenia. LBW correlates with reduced muscle mass, grip strength, and lean body mass in adulthood, increasing the risk of sarcopenia. Chronic inflammation (inflammaging) and mitochondrial dysfunction contribute to sarcopenia, with LBW linked to increased oxidative stress and dysfunction. Disrupted circadian rhythms, regulated by genes such as BMAL1 and CLOCK, are associated with both LBW and sarcopenia, impacting lipid metabolism, muscle mass, and the ageing process. Early-life exposures, including LBW, induce epigenetic modifications like DNA methylation (DNAm) and histone changes, playing a pivotal role in sarcopenia development. Genome-wide studies have identified candidate genes and variants associated with lean body mass, muscle weakness, and sarcopenia, providing insights into genetic factors contributing to the disorder. LBW emerges as a potential early predictor of sarcopenia development, reflecting the impact of intrauterine exposures on long-term health outcomes. Understanding the complex interplay between LBW with inflammaging, mitochondrial dysfunction, circadian disruption, and epigenetic factors is essential for elucidating the pathogenesis of sarcopenia and developing targeted interventions. Future research on GWAS and the underlying mechanisms of LBW-associated sarcopenia is warranted to inform preventive strategies and improve public health outcomes.


Assuntos
Recém-Nascido de Baixo Peso , Sarcopenia , Humanos , Sarcopenia/etiologia , Sarcopenia/genética , Feminino , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Recém-Nascido , Epigênese Genética , Estudo de Associação Genômica Ampla
4.
Front Aging Neurosci ; 16: 1354025, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524114

RESUMO

The growing phenomenon of population aging is redefining demographic dynamics, intensifying age-related conditions, especially dementia, projected to triple by 2050 with an enormous global economic burden. This study investigates visual arts-mediated Cognitive Activation Therapy (CAT) as a non-pharmacological CAT intervention targets both biological aging [leukocyte telomere length (LTL), DNA methylation age (DNAmAge)] and cognitive functionality. Aligning with a broader trend of integrating non-pharmacological approaches into dementia care. The longitudinal study involved 20 patients with mild to moderate neurocognitive disorders. Cognitive and functional assessments, and biological aging markers -i.e., LTL and DNAmAge- were analyzed before and after CAT intervention. Change in LTL was positively correlated with days of treatment (p =0.0518). LTL significantly elongated after intervention (p =0.0269), especially in men (p =0.0142), correlating with younger age (p =0.0357), and higher education (p =0.0008). DNAmAge remained instead stable post-treatment. Cognitive and functional improvements were observed for Copy of complex geometric figure, Progressive Silhouettes, Position Discrimination, Communication Activities of Daily Living-Second edition, Direct Functional Status (p < 0.0001) and Object decision (p =0.0594), but no correlations were found between LTL and cognitive gains. Visual arts-mediated CAT effectively mitigates cellular aging, especially in men, by elongating LTL. These findings underscore the potential of non-pharmacological interventions in enhancing cognitive and functional status and general well-being in dementia care. Further research with larger and longer-term studies is essential for validation.

5.
Ageing Res Rev ; 95: 102227, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38346506

RESUMO

Astronauts returning from space missions often exhibit health issues mirroring age-related conditions, suggesting spaceflight as a potential driver of biological ageing and age-related diseases. To unravel the underlying mechanisms of these conditions, this comprehensive review explores the impact of the space "exposome" on the twelve hallmarks of ageing. Through a meticulous analysis encompassing both space environments and terrestrial analogs, we aim to decipher how different conditions influence ageing hallmarks. Utilizing PubMed, we identified 189 studies and 60 meet screening criteria. Research on biological ageing in space has focused on genomic instability, chronic inflammation, and deregulated nutrient sensing. Spaceflight consistently induces genomic instability, linked to prolonged exposure to ionizing radiation, triggers pro-inflammatory and immune alterations, resembling conditions in isolated simulations. Nutrient sensing pathways reveal increased systemic insulin-like growth-factor-1. Microbiome studies indicate imbalances favoring opportunistic species during spaceflight. Telomere dynamics present intriguing patterns, with lengthening during missions and rapid shortening upon return. Despite a pro-ageing trend, some protective mechanisms emerge. Countermeasures, encompassing dietary adjustments, prebiotics, postbiotics, symbiotics, tailored exercises, meditation, and anti-inflammatory supplements, exhibit potential. Spaceflight's impact on ageing is intricate, with diverse findings challenging established beliefs. Multidisciplinary studies provide guidance for future research in this field.


Assuntos
Voo Espacial , Humanos , Astronautas , Envelhecimento , Terapia por Exercício , Instabilidade Genômica
6.
Vaccines (Basel) ; 11(12)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38140174

RESUMO

Introduction: The impact of long-COVID-19 syndrome is rather variable, since it is influenced by several residual confounders. This study aimed to investigate the prevalence of long COVID-19 in healthcare workers (HCWs) from four university hospitals in north-eastern Italy: Trieste, Padua, Verona, and Modena-Reggio Emilia. Methods: During the period June 2022-August 2022, HCWs were surveyed for past COVID-19 infections, medical history, and any acute as well as post-COVID-19 symptoms. The prevalence of long COVID-19 was estimated at 30-60 days or 61+ days since first negative swab following first and second COVID-19 episode. Furthermore, the risk of long COVID-19 was investigated by multivariable logistic regression. Results were expressed as the adjusted odds ratio (aOR) with a 95% confidence interval (95%CI). Results: 5432 HCWs returned a usable questionnaire: 2401 were infected with SARS-CoV-2 at least once, 230 were infected at least twice, and 8 were infected three times. The prevalence of long COVID-19 after a primary COVID-19 infection was 24.0% at 30-60 days versus 16.3% at 61+ days, and 10.5% against 5.5% after the second SARS-CoV-2 event. The most frequent symptoms after a first COVID-19 event were asthenia (30.3%), followed by myalgia (13.7%), cough (12.4%), dyspnea (10.2%), concentration deficit (8.1%), headache (7.3%), and anosmia (6.5%), in decreasing order of prevalence. The risk of long COVID-19 at 30-60 days was significantly higher in HCWs hospitalized for COVID-19 (aOR = 3.34; 95%CI: 1.62; 6.89), those infected with SARS-CoV-2 during the early pandemic waves-namely the Wuhan (aOR = 2.16; 95%CI: 1.14; 4.09) or Alpha (aOR= 2.05; 95%CI: 1.25; 3.38) transmission periods-and progressively increasing with viral shedding time (VST), especially 15+ days (aOR = 3.20; 95%CI: 2.07; 4.94). Further determinants of long COVID-19 at 30-60 days since primary COVID-19 event were female sex (aOR = 1.91; 95%CI: 1.30; 2.80), age >40 years, abnormal BMI, or administrative services (reference category). In contrast, HCWs vaccinated with two doses before their primary infection (aOR = 0.57; 95%CI: 0.34; 0.94), undergraduate students, or postgraduate medical trainees were less likely to experience long COVID-19 at 30-60 days. Apart from pandemic waves, the main determinants of long COVID-19 at 30-60 days were confirmed at 61+ days. Conclusions: The risk of long COVID-19 following primary infection increased with the severity of acute disease and VST, especially during the initial pandemic waves, when more virulent viral strains were circulating, and susceptibility to SARS-CoV-2 was higher since most HCWs had not been infected yet, COVID-19 vaccines were still not available, and/or vaccination coverage was still building up. The risk of long COVID-19 therefore decreased inversely with humoral immunity at the individual level. Nevertheless, the prevalence of long COVID-19 was remarkably lower after SARS-CoV-2 reinfections regardless of vaccination status, suggesting that hybrid humoral immunity did not increase protection against the syndrome compared to immunity mounted by either natural infection or vaccination separately. Since the risk of long COVID-19 is currently low with Omicron and patients who developed the syndrome following SARS-CoV-2 infection in the early pandemic waves tend to return to a state of full health with time, a cost-effective approach to screen post-COVID-19 symptoms during the Omicron time could be restricted to vulnerable individuals developing severe disease and/or with prolonged VST.

7.
Vaccines (Basel) ; 11(10)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37896931

RESUMO

BACKGROUND: The effectiveness of the immunity provided by SARS-CoV-2 vaccines is an important public health issue. We analyzed the determinants of 12-month serology in a multicenter European cohort of vaccinated healthcare workers (HCW). METHODS: We analyzed the sociodemographic characteristics and levels of anti-SARS-CoV-2 spike antibodies (IgG) in a cohort of 16,101 vaccinated HCW from eleven centers in Germany, Italy, Romania, Slovakia and Spain. Considering the skewness of the distribution, the serological levels were transformed using log or cubic standardization and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log or cubic antibody level and the corresponding 95% confidence interval (CI) for different factors and combined them in random-effects meta-analyses. RESULTS: We included 16,101 HCW in the analysis. A high antibody level was positively associated with age (RR = 1.04, 95% CI = 1.00-1.08 per 10-year increase), previous infection (RR = 1.78, 95% CI 1.29-2.45) and use of Spikevax [Moderna] with combinations compared to Comirnaty [BioNTech/Pfizer] (RR = 1.07, 95% CI 0.97-1.19) and was negatively associated with the time since last vaccine (RR = 0.94, 95% CI 0.91-0.98 per 30-day increase). CONCLUSIONS: These results provide insight about vaccine-induced immunity to SARS-CoV-2, an analysis of its determinants and quantification of the antibody decay trend with time since vaccination.

8.
Environ Health ; 22(1): 27, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36927494

RESUMO

BACKGROUND: Aging represents a serious health and socioeconomic concern for our society. However, not all people age in the same way and air pollution has been shown to largely impact this process. We explored whether polycyclic aromatic hydrocarbons (PAHs), excellent fossil and wood burning tracers, accelerate biological aging detected by lymphocytes DNA methylation age (DNAmAge) and telomere length (TL), early nuclear DNA (nDNA) hallmarks of non-mitotic and mitotic cellular aging, and mitochondrial DNA copy number (mtDNAcn). METHODS: The study population consisted of 49 male noncurrent-smoking coke-oven workers and 44 matched controls. Occupational and environmental sources of PAH exposures were evaluated by structured questionnaire and internal dose (urinary 1-pyrenol). We estimated Occup_PAHs, the product of 1-pyrenol and years of employment as coke-oven workers, and Environ_PAHs, from multiple items (diet, indoor and outdoor). Biological aging was determined by DNAmAge, via pyrosequencing, and by TL and mtDNAcn, via quantitative polymerase chain reaction. Genomic instability markers in lymphocytes as target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei), gene-specific (p53, IL6 and HIC1) and global (Alu and LINE-1 repeats) DNA methylation, and genetic polymorphisms (GSTM1) were also evaluated in the latent variable nDNA_changes. Structural equation modelling (SEM) analysis evaluated these multifaceted relationships. RESULTS: In univariate analysis, biological aging was higher in coke-oven workers than controls as detected by higher percentage of subjects with biological age older than chronological age (AgeAcc ≥ 0, p = 0.007) and TL (p = 0.038), mtDNAcn was instead similar. Genomic instability, i.e., genotoxic and epigenetic alterations (LINE-1, p53 and Alu) and latent variable nDNA_changes were higher in workers (p < 0.001). In SEM analysis, DNAmAge and TL were positively correlated with Occup_PAHs (p < 0.0001). Instead, mtDNAcn is positively correlated with the latent variable nDNA_changes (p < 0.0001) which is in turn triggered by Occup_PAHs and Environ_PAHs. CONCLUSIONS: Occupational PAHs exposure influences DNAmAge and TL, suggesting that PAHs target both non-mitotic and mitotic mechanisms and made coke-oven workers biologically older. Also, differences in mtDNAcn, which is modified through nDNA alterations, triggered by environmental and occupational PAH exposure, suggested a nuclear-mitochondrial core-axis of aging. By decreasing this risky gerontogenic exposure, biological aging and the consequent age-related diseases could be prevented.


Assuntos
Coque , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Masculino , Hidrocarbonetos Policíclicos Aromáticos/análise , Biomarcadores Ambientais , Coque/análise , Proteína Supressora de Tumor p53 , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Envelhecimento
9.
Regul Toxicol Pharmacol ; 139: 105369, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36870410

RESUMO

Several toxicological and epidemiological studies were published during the last five decades on non-sugar sweeteners (NSS) and cancer. Despite the large amount of research, the issue still continues to be of interest. In this review, we provided a comprehensive quantitative review of the toxicological and epidemiological evidence on the possible relation between NSS and cancer. The toxicological section includes the evaluation of genotoxicity and carcinogenicity data for acesulfame K, advantame, aspartame, cyclamates, saccharin, steviol glycosides and sucralose. The epidemiological section includes the results of a systematic search of cohort and case-control studies. The majority of the 22 cohort studies and 46 case-control studies showed no associations. Some risks for bladder, pancreas and hematopoietic cancers found in a few studies were not confirmed in other studies. Based on the review of both the experimental data on genotoxicity or carcinogenicity of the specific NSS evaluated, and the epidemiological studies it can be concluded that there is no evidence of cancer risk associated to NSS consumption.


Assuntos
Neoplasias , Edulcorantes , Humanos , Edulcorantes/toxicidade , Açúcares , Sacarina , Aspartame/toxicidade , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-36613152

RESUMO

Healthcare workers (HCWs) represent a population with a significant burden of paucisymptomatic COVID-19, as the general population. We evaluated autonomic nervous system activity by means of heart rate variability (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings were obtained 30 days (IQR 5.25-55.75) after a negative naso-pharyngeal swab for SARS-CoV-2 in 44 cases and compared with ECGs of 44 controls with similar age and sex distribution. Time and frequency domain HRV were evaluated. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded. Frequency domain HRV analysis showed a significantly higher low/high-frequency power ratio (LF/HF) in the case study compared with controls (t = 2.84, p = 0.006). In time domain HRV analysis, mean standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were significantly lower for cases compared with controls (t = -2.64, p = 0.01 and t = -3.27, p = 0.002, respectively). In the post-acute phase of infection, SARS-CoV-2 produces an autonomic imbalance mirrored by a reduction in HRV. These results are consistent with epidemiological data that suggest a higher risk of acute cardiovascular complications in the first 30 days after COVID-19 infection.


Assuntos
Doenças do Sistema Nervoso Autônomo , COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Sistema Nervoso Autônomo/fisiologia , Eletrocardiografia , Frequência Cardíaca/fisiologia
11.
Vaccines (Basel) ; 10(8)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-36016081

RESUMO

BACKGROUND: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. METHODS: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). RESULTS: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). CONCLUSION: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated.

12.
Front Med (Lausanne) ; 9: 832411, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402460

RESUMO

The biological age of an organ may represent a valuable tool for assessing its quality, especially in the elder. We examined the biological age of the kidneys [right (RK) and left kidney (LK)] and blood leukocytes in the same subject and compared these to assess whether blood mirrors kidney biological aging. Biological age was studied in n = 36 donors (median age: 72 years, range: 19-92; male: 42%) by exploring mitotic and non-mitotic pathways, using telomere length (TL) and age-methylation changes (DNAmAge) and its acceleration (AgeAcc). RK and LK DNAmAge are older than blood DNAmAge (RK vs. Blood, p = 0.0271 and LK vs. Blood, p = 0.0245) and RK and LK AgeAcc present higher score (this mean the AgeAcc is faster) than that of blood leukocytes (p = 0.0271 and p = 0.0245) in the same donor. TL of RK and LK are instead longer than that of blood (p = 0.0011 and p = 0.0098) and the increase in Remuzzi-Karpinski score is strongly correlated with kidney TL attrition (p = 0.0046). Finally, blood and kidney TL (p < 0.01) and DNAmAge (p < 0.001) were correlated. These markers can be evaluated in further studies as indicators of biological age of donor organ quality and increase the usage of organs from donors of advanced age therefore offering a potential translational research inkidney transplantation.

13.
Clin Epigenetics ; 14(1): 20, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130936

RESUMO

BACKGROUND: Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant complications, such as allograft rejection, chronic renal allograft dysfunction, and cutaneous squamous cell carcinoma, have a suboptimal predictive value. DNA methylation is an epigenetic modification that directly affects gene expression and plays an important role in processes such as ischemia/reperfusion injury, fibrosis, and alloreactive immune response. Novel techniques can quickly assess the DNA methylation status of multiple loci in different cell types, allowing a deep and interesting study of cells' activity and function. Therefore, DNA methylation has the potential to become an important biomarker for prediction and monitoring in kidney transplantation. PURPOSE OF THE STUDY: The aim of this study was to evaluate the role of DNA methylation as a potential biomarker of graft survival and complications development in kidney transplantation. MATERIAL AND METHODS: A systematic review of several databases has been conducted. The Newcastle-Ottawa scale and the Jadad scale have been used to assess the risk of bias for observational and randomized studies, respectively. RESULTS: Twenty articles reporting on DNA methylation as a biomarker for kidney transplantation were included, all using DNA methylation for prediction and monitoring. DNA methylation pattern alterations in cells isolated from different tissues, such as kidney biopsies, urine, and blood, have been associated with ischemia-reperfusion injury and chronic renal allograft dysfunction. These alterations occurred in different and specific loci. DNA methylation status has also proved to be important for immune response modulation, having a crucial role in regulatory T cell definition and activity. Research also focused on a better understanding of the role of this epigenetic modification assessment for regulatory T cells isolation and expansion for future tolerance induction-oriented therapies. CONCLUSIONS: Studies included in this review are heterogeneous in study design, biological samples, and outcome. More coordinated investigations are needed to affirm DNA methylation as a clinically relevant biomarker important for prevention, monitoring, and intervention.


Assuntos
Biomarcadores/análise , Metilação de DNA/genética , Transplante de Rim/normas , Metilação de DNA/fisiologia , Rejeição de Enxerto/genética , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/cirurgia , Transplante de Rim/métodos , Medição de Risco/métodos
14.
Front Med (Lausanne) ; 8: 753819, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805220

RESUMO

The battle against the new coronavirus that continues to kill millions of people will be still long. Novel strategies are demanded to control infection, mitigate symptoms and treatment of COVID-19. This is even more imperative given the long sequels that the disease has on the health of the infected. The discovery that S protein includes two ankyrin binding motifs (S-ARBMs) and that the transient receptor potential vanilloid subtype 1 (TRPV-1) cation channels contain these ankyrin repeat domains (TRPs-ARDs) suggest that TRPV-1, the most studied member of the TRPV channel family, can play a role in binding SARS-CoV-2. This hypothesis is strengthened by studies showing that other respiratory viruses bind the TRPV-1 on sensory nerves and epithelial cells in the airways. Furthermore, the pathophysiology in COVID-19 patients is similar to the effects generated by TRPV-1 stimulation. Lastly, treatment with agonists that down-regulate or inactivate TRPV-1 can have a beneficial action on impaired lung functions and clearance of infection. In this review, we explore the role of the TRPV-1 channel in the infection, susceptibility, pathogenesis, and treatment of COVID-19, with the aim of looking at novel strategies to control infection and mitigate symptoms, and trying to translate this knowledge into new preventive and therapeutic interventions.

15.
J Clin Med ; 10(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34441997

RESUMO

Leukocyte telomere length (LTL) represents a key integrating component of the cumulative effects of environmental, lifestyle, and genetic factors. A question, however, remains on whether LTL can be considered predictive for a longer and healthier life. Within the elderly prospective TRELONG cohort (n = 612), we aimed to investigate LTL as a predictor of longevity and identify the main determinants of LTL among many different factors (physiological and lifestyle characteristics, physical performance and frailty measures, chronic diseases, biochemical measurements and apolipoprotein E genotyping). We found an ever-increasing relationship between LTL quartiles and survival. Hazard ratio analysis showed that for each unit increase in LTL and Short Physical Performance Battery (SPPB) scores, the mortality risk was reduced by 22.41% and 8.78%, respectively. Conversely, male gender, Charlson Comorbidity Index, and age threatened survival, with mortality risk growing by 74.99%, 16.57% and 8.5%, respectively. Determinants of LTL elongation were SPPB scores (OR = 1.1542; p = 0.0066) and years of education (OR = 1.0958; p = 0.0065), while male gender (OR = 0.4388; p = 0.0143) and increased Disease Count Index (OR = 0.6912; p = 0.0066) were determinants of LTL attrition. Longer LTL predicts a significant survival advantage in elderly people. By identifying determinants of LTL elongation, we provided additional knowledge that could offer a potential translation into prevention strategies.

16.
Front Med (Lausanne) ; 8: 690312, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368190

RESUMO

Aging is the predominant risk factor for most degenerative diseases, including chronic obstructive pulmonary disease (COPD). This process is however very heterogeneous. Defining the biological aging of individual tissues may contribute to better assess this risky process. In this study, we examined the biological age of induced sputum (IS) cells, and peripheral blood leukocytes in the same subject, and compared these to assess whether biological aging of blood leukocytes mirrors that of IS cells. Biological aging was assessed in 18 COPD patients (72.4 ± 7.7 years; 50% males). We explored mitotic and non-mitotic aging pathways, using telomere length (TL) and DNA methylation-based age prediction (DNAmAge) and age acceleration (AgeAcc) (i.e., difference between DNAmAge and chronological age). Data on demographics, life style and occupational exposure, lung function, and clinical and blood parameters were collected. DNAmAge (67.4 ± 5.80 vs. 61.6 ± 5.40 years; p = 0.0003), AgeAcc (-4.5 ± 5.02 vs. -10.8 ± 3.50 years; p = 0.0003), and TL attrition (1.05 ± 0.35 vs. 1.48 ± 0.21 T/S; p = 0.0341) are higher in IS cells than in blood leukocytes in the same patients. Blood leukocytes DNAmAge (r = 0.927245; p = 0.0026) and AgeAcc (r = 0.916445; p = 0.0037), but not TL, highly correlate with that of IS cells. Multiple regression analysis shows that both blood leukocytes DNAmAge and AgeAcc decrease (i.e., younger) in patients with FEV1% enhancement (p = 0.0254 and p = 0.0296) and combined inhaled corticosteroid (ICS) therapy (p = 0.0494 and p = 0.0553). In conclusion, new findings from our work reveal a differential aging in the context of COPD, by a direct quantitative comparison of cell aging in the airway with that in the more accessible peripheral blood leukocytes, providing additional knowledge which could offer a potential translation into the disease management.

17.
Environ Health ; 19(1): 128, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272294

RESUMO

BACKGROUND: Further knowledge on modifiable aging risk factors is required to mitigate the increasing burden of age-related diseases in a rapidly growing global demographic of elderly individuals. We explored the effect of everyday exposure to polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution, on cellular biological aging. This was determined via the analysis of leukocyte telomere length (LTL), mitochondrial DNA copy number (LmtDNAcn), and by the formation of anti-benzo[a]pyrene diolepoxide (B[a]PDE-DNA) adducts. METHODS: The study population consisted of 585 individuals living in North-East Italy. PAH exposure (diet, indoor activities, outdoor activities, traffic, and residential exposure) and smoking behavior were assessed by questionnaire and anti-B[a]PDE-DNA by high-performance-liquid-chromatography. LTL, LmtDNAcn and genetic polymorphisms [glutathione S-transferase M1 and T1 (GSTM1; GSTT1)] were measured by polymerase chain reaction. Structural equation modelling analysis evaluated these complex relationships. RESULTS: Anti-B[a]PDE-DNA enhanced with PAH exposure (p = 0.005) and active smoking (p = 0.0001), whereas decreased with detoxifying GSTM1 (p = 0.021) and in females (p = 0.0001). Subsequently, LTL and LmtDNAcn reduced with anti-B[a]PDE-DNA (p = 0.028 and p = 0.018), particularly in males (p = 0.006 and p = 0.0001). Only LTL shortened with age (p = 0.001) while elongated with active smoking (p = 0.0001). Besides this, the most significant determinants of PAH exposure that raised anti-B[a]PDE-DNA were indoor and diet (p = 0.0001), the least was outdoor (p = 0.003). CONCLUSION: New findings stemming from our study suggest that certain preventable everyday life exposures to PAHs reduce LTL and LmtDNAcn. In particular, the clear association with indoor activities, diet, and gender opens new perspectives for tailored preventive measures in age-related diseases. CAPSULE: Everyday life exposure to polycyclic aromatic hydrocarbons reduces leukocyte telomere length and mitochondrial DNA copy number through anti-B[a]PDE-DNA adduct formation.


Assuntos
Envelhecimento , Exposição Ambiental , Poluentes Ambientais , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Adutos de DNA , Variações do Número de Cópias de DNA , DNA Mitocondrial , Dieta , Biomarcadores Ambientais , Feminino , Glutationa Transferase/genética , Humanos , Itália , Leucócitos , Masculino , Pessoa de Meia-Idade , Fumar , Inquéritos e Questionários , Telômero
18.
Artigo em Inglês | MEDLINE | ID: mdl-33092014

RESUMO

Background: A national database of work-related injuries has been established in Italy since 2002, collecting information on the injured person, his/her work tasks, the workplace and the risk factors contributing to incident dynamics, according to a model called Infor.Mo. Methods: A descriptive study of occupational fatal injuries, excluding work-related fatal traffic injuries, that occurred in Italy from 2002 to 2016 (15 years) was performed. Results: Among 4874 victims involved, all were males, mainly >51 years of age (43.2%), predominantly self-employed (27.8%) or workers with non-standard contracts (25%). About 18.4% and 17.3% of fatal events occurred in micro-enterprises belonging to, respectively, construction and agriculture. A wide range of nationalities (59 countries in addition to Italy) was identified. Overall, 18.9% of work-related fatal injuries were due to some form of hazardous energy-mechanical, thermal, electrical or chemical-that was normally present in the workplace. Workers' falls from height (33.5%), heavy loads falling on workers from height (16.7%) and vehicles exiting their route and overturning (15.9%) were the events causing the greatest proportion of occupational fatal injuries in the present study (from 2002 to 2016) and in the initial pilot phase, focused on years 2002-2004, with a similar distribution of fatal events between the two time periods. The activity of the injured person made up 43.3% of 9386 risk factors identified in 4874 fatalities. Less common risk factors were related to work equipment (20.2%), work environment (14.9%), third-party activity (9.8%), personal protective equipment/clothing (8.0%) and materials (3.7%). The activity of the injured person remained the most relevant contributing factor even when the incident was caused by two or more risk factors. Discussion: Occupational fatal injuries occurred mainly in small size firms (up to nine employees) in hazardous workplaces. Small companies, which account for 68% (2888/4249) of all firms in the present study, generally have fewer resources to remain current with the continuously evolving health and safety at work regulations; moreover, these firms tend to be less compliant with health and safety at work regulations since they are less likely to be inspected by occupational vigilance services. Perspectives: An approach being introduced in Italy relies on the use of economic incentives to promote safe and healthy workplaces. The comparison of pre-intervention and post-intervention rates of work-related injuries by means of interrupted time series analyses could detect whether the intervention will have an effect significantly greater than the underlying secular trend.


Assuntos
Acidentes de Trabalho , Traumatismos Ocupacionais , Acidentes de Trabalho/mortalidade , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Traumatismos Ocupacionais/mortalidade , Local de Trabalho
19.
Sci Rep ; 10(1): 15163, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938990

RESUMO

A neurogenic pathway, involving airway TRPV-1, has been implicated in acute cardiovascular events occurring after peaks of air pollution. We tested whether inhaled prostaglandin-E2 (PGE2) and bradykinin (BK) regulate TRPV-1 activity in vivo by changing cough response to capsaicin (CPS) and affecting heart rate variability (HRV), while also taking into account the influence of TRPV-1 polymorphisms (SNPs). Moreover, we assessed the molecular mechanism of TRPV-1 modulation in vitro. Seventeen healthy volunteers inhaled 100 µg PGE2, 200 µg BK or diluent in a randomized double-blind fashion. Subsequently, the response to CPS was assessed by cough challenge and the sympathetic activity by HRV, expressed by low (nLF) and high (nHF) normalized frequency components, as well as nLF/nHF ratio. Intracellular [Ca2+] was measured in HeLa cells, transfected with wild-type TRPV-1, pre-treated with increasing doses of PGE2, BK or diesel exhaust particulate (DEP), after CPS stimulation. Six functional TRPV-1 SNPs were characterized in DNA from each subject. Inhalation of PGE2 and BK was associated with significant increases in cough response induced by 30 µM of CPS (cough number after PGE2 = 4.20 ± 0.42; p < 0.001, and after BK = 3.64 ± 0.37; p < 0.01), compared to diluent (2.77 ± 0.29) and in sympathetic activity (nLF/nHF ratio after PGE2 = 6.1; p < 0.01, and after BK = 4.2; p < 0.05), compared to diluent (2.5-3.3). No influence of SNPs was observed on autonomic regulation and cough sensitivity. Unlike PGE2 and BK, DEP directly activated TRPV-1. Inhalation of PGE2 and BK sensitizes TRPV-1 and is associated with autonomic dysregulation of cardiac rhythm in healthy subjects.


Assuntos
Bradicinina/farmacologia , Tosse/fisiopatologia , Dinoprostona/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Canais de Cátion TRPV/efeitos dos fármacos , Canais de Cátion TRPV/fisiologia , Administração por Inalação , Adulto , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/fisiologia , Bradicinina/administração & dosagem , Capsaicina/administração & dosagem , Capsaicina/efeitos adversos , Dinoprostona/administração & dosagem , Método Duplo-Cego , Feminino , Células HeLa , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Canais de Cátion TRPV/genética
20.
Sci Rep ; 10(1): 10752, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32612244

RESUMO

Chronological age represents the main factor in donor selection criteria for organ transplantation, however aging is very heterogeneous. Defining the biological aging of individual organs may contribute to supporting this process. In this study we examined the biological age of the heart [right (RA)/left atrium (LA)] and peripheral blood leucocytes in the same subject, and compared these to assess whether blood mirrors cardiac biological aging. Biological aging was studied in 35 donors (0.4-72 years) by exploring mitotic and non-mitotic pathways, using telomere length (TL) and age-dependent methylation changes in certain CpG loci (DNAmAge). Heart non-mitotic DNAmAge was strongly younger than that of both blood (- 10 years, p < 0.0001) and chronological age (- 12 years, p < 0.0001). Instead, heart and blood mitotic age (TL) were similar, and there was no difference in DNAmAge and TL between RA and LA. DNAmAge negatively correlated with TL in heart and blood (p ≤ 0.01). Finally, blood and heart TL (p < 0.01) and DNAmAge (p < 0.0001) were correlated. Therefore, blood can be a proxy indicator of heart biological age. While future investigation on post-transplant graft performance in relation to biological aging is still needed, our study could contribute to opening up novel basic and clinical research platforms in the field of organ transplantation.


Assuntos
Envelhecimento , Coração/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Biomarcadores/metabolismo , Senescência Celular , Criança , Pré-Escolar , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Feminino , Átrios do Coração , Transplante de Coração , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mitose , Seleção de Pacientes , Telômero , Obtenção de Tecidos e Órgãos/métodos , Adulto Jovem
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